3-Halo-3-methylcephams are known in the art to be useful in the synthesis of 3-methyl-3-cephem antibiotics. Several processes have been developed for the preparation of 3-halo-3-methylcephams. Micetich and Morin, for instance, in Tetrahedron Letters, No. 13, pp. 979-982, 1976, disclosed the reaction of a thiazoline azetidinone with iodine and water to give the corresponding 3-iodo-3-methylcepham. These authors reported that the reaction was not general in that bromine and chlorine failed to behave as did iodine.
Foglio et al., in U.S. Pat. No. 4,018,776, report an iodination process comprising reaction of a thiazoline azetidinone with iodine in the presence of a heavy metal oxide or a free radical initiator such as a peroxide. Nadelman et al., in U.S. Pat. No. 3,932,398, disclose the reaction of a penicillin sulfoxide with a neutral or basic catalyst in a polyhaloalkane solvent to give a 3-halo-3-methylcepham. More recently, Yoshioka et al., in U.S. Pat. No. 4,183,855, disclosed the synthesis of certain 3-halo-3-methyl-1-oxacephams from oxazoline azetidinone derivatives.
An object of this invention is to provide a new process for preparing 3-bromo-3-methylcephams.